ADRENAL GLAND

Lecture ObjectivesAt the end of this lecture, the student should be able to:• Enumerate the adrenocortical and adrenomedullary

hormones• Describe the chemical nature, source and actions of

mineralocorticoids• Describe the chemical nature, source and actions of

Glucocorticoids• Describe the chemical nature, source and actions of

adrenal androgens• Describe the feed back control of adrenocortical

hormones.

ADRENAL GLANDEach adrenal gland is composed of two endocrine organs:

(A) Adrenal medulla (The inner portion) :

• It secretes Adrenaline, Noradrenaline & Dopamine in to blood.

(B) Adrenal cortex (The three outer layers):

• Zona Glomerulosa: the outermost layer that secretes Mineralocorticoids (Aldosterone).

• Zona Fasciculata: secretes Glucocorticoids (Cortisol).

• Zona Reticularis: the innermost layer that secretes Sex hormones (dehydroepiandrosterone = DHEA).

The steroids of adrenal cortex1. Mineralocorticoids, mainly aldosterone,

influence minerals (electrolytes) balance, specifically Na+ & K+ balance.

2. Glucocorticoids, primarily cortisol, play a major role in glucose metabolism as well as in protein and lipid metabolism and in adaptation to stress.

3. Sex hormones, are similar to those produced by gonads. The most abundant and physiologically important of the adrenal androgen is dehydroepiandrosterone (DHEA).

Mechanism of action of Steroids

Steroidogenic pathways for the major steroid hormones

1 - MINERALOCORTICOIDSALDOSTERONE

• Functions:1) ↑ Reabsorption of Na+ from distal renal tubules.2) ↑ Excretion of K+ from distal renal tubules.3) ↑ Excretion of H+ ions from distal renal tubules.4) ↑ Water reabsorption along with Na+.5) Na+ content of sweat, saliva and other secretions.6) Acts as a long-term regulator of blood pressure

CONTROL OF ALDOSTERONE SECRETIONWithout aldosterone, a person rapidly dies from

circulatory shock because of the marked fall in plasma volume caused by excessive losses of H2O-holding Na+.

Aldosterone secretion is controlled by:1- ↓ Plasma Na+ or ↑ K+:• Plasma Na+ by 10 % or plasma K+ by 10 %

stimulate synthesis and release of aldosterone by a direct action.

2- Secretion of renin & Angiotensin II formation:• Angiotensin II & III stimulate zona glomerulosa to

produce Aldosterone.

CONTROL OF ALDOSTERONE SECRETION3- ACTH:• ACTH is not a major factor in control of aldosterone.• ACTH in large dose (greater than the dose that

stimulates maximum cortisol secretion) transient in aldosterone.

4- Atrial Natriuretic Factor (ANF):• Inhibits aldosterone and renin secretion in a negative

feedback manner.• ANP decreases responsiveness of zona glomerulosa to

stimuli that normally increase aldosterone secretion.

HYPERALDOSTERONISM

• Primary hyperaldosteronism (Conn’s syndrome):– Cause:• Adrenal tumor of aldosterone –secreting cells

• Secondary hyperaldosteronism:– Cause:• inappropriately high activity of the renin-angiotensin-

aldosterone system

1- PRIMARY ALDOSTERONISM (CONN’S SYNDROME)

• Aldosterone-secreting tumors of adrenal cortex aldosterone.

• Na+ retention hypertension.• K+ excretion hypokalemia• Alkalosis tetany.• Polyuria due to renal damage and loss of

concentrating ability (= Hypokalaemic nephropathy). • No edema (due to Aldosterone escape

phenomenon).

2- SECONDARY ALDOSTERONISM

• Renal ischemia renin Angiotensin II aldosterone.

• Or Hyperplasia of JGA in kidney renin• All signs of aldosterone excess appear & edema

occurs.

2- Glucocorticoids• Cortisol, the primary glucocorticoid, plays an

important role in carbohydrate, protein, and fat metabolism; executes significant permissive actions for other hormonal activities; and helps people resist stress.

• It is secreted from zona fasciculata. • Cortisol has anti-stress & anti-shock effects.• Excess cortisol has anti-inflammatory & anti-

allergic effects.

Functions of cortisol1) Protein metabolism:• It inhibits amino acid uptake and protein synthesis in

extrahepatic tissues.• Catabolic in muscle, skin and bone.• Excess cortisol severe muscle wasting.

2) CHO metabolism: ↑ Blood glucose level by: • ↓ Tissue uptake of glucose.• ↓ Conversion of glucose to glucose-6-phosphate (anti-

insulin action).• ↑ gluconeogenesis in liver.• Excess cortisol diabetogenic.

Functions of cortisol3) Fat metabolism:• Mobilization of fat from fat depots to supply energy

(Lipolytic ketogenic).• Excess cortisol ketosis.

4) Cardiovascular function: • Increase myocardial contractility and

vasoconstriction due to enhancement of catecholamine effects (permissive effects of cortisol).

Functions of cortisol5) Anti-stress: • Activate energy metabolism. • In severe physical or mental stress, cortisol plasma

conc. remains at a very high level (up to 10 times the normal value) throughout the day.

6) Anti-allergic: • Cortisol inhibits allergic responses.• ↓ Histamine synthesis in mast cells and basophils • ↓ Kinin synthesis.

Functions of cortisol7) Anti-inflammatory:• Cortisol inhibits all stages of inflammatory process.• It has a stabilizing action on lysosomal membranes of

leucocytes. • ↓inflammatory chemical mediators as prostaglandins

& Interleukins.• It suppresses migration of neutrophils.• It inhibits proliferation of fibroblasts in wound repair

Functions of cortisol8) Cortisol impedes development of cartilage:• ↓ Absorption of Ca++ from GIT by antagonizing effect of

vitamin D.• ↑ Ca++ loss in urine.• Excess cortisol osteoporosis of bones especially

vertebrae.

9) Immunosuppressive:• Cortisol inhibits normal immune response.• ↓ Circulating lymphocytes, basophils and eosinophils.• ↓ Antibody production.• Disadvantage: it causes spread of infection (as TB).• Advantage: It is used in treatment of autoimmune disorders.

Functions of cortisol10) On GIT: • Cortisol increases gastric acidity.• Excess cortisol peptic ulcer.

11) On water & electrolytes:• Excess cortisol Na+ & water retention and K+

excretion (aldosterone like action).

12) On CNS:• Increase EEG activity.• Excess cortisol psychosis.

Control of cortisol secretion

–ve feedback system for cortisol maintains the level of cortisol secretion relatively constant around the set point.

Cortisol produces -ve feedback to inhibit hypothalamic CRH and anterior pituitary ACTH.

Plasma cortisol concentration displays a characteristic circadian rhythm, with the highest level occurring in the morning and the lowest level at night.

Adrenal sex hormones

• Adrenal cortex secretes small amounts of androgens, estrogens & progesterone.

• Under normal circumstances, adrenal androgens and estrogens are not sufficiently abundant or powerful to induce masculinizing or feminizing effects, respectively.

• Dehydroepiandrosterone (DHEA) is a weak androgen that governs androgen-dependent processes in the female such as:

1- Growth of pubic and axillary hair

2- Enhancement of the pubertal growth spurt

3- Development and maintenance of the female sex drive.